The artificial sweetener 4,1', 6'-trichloro-4,1', 6'-trideoxygalactosucrose ("sucralose") is derived from sucrose by replacing the hydroxyls in the 4, 1', and 6' positions with chlorine. In the process of making the compound, the stereo configuration at the 4 position is reversed. Therefore, sucralose is a galactosucrose having the following molecular structure: ##STR1##
The direction of the chlorine atoms to only the desired positions is a major synthesis problem because the hydroxyls that are replaced are of differing reactivity; two are primary and one is secondary. The synthesis is further complicated by the fact that the primary hydroxyl in the 6 position is unsubstituted in the final product.
A number of different synthetic routes for the preparation of sucralose have been developed in which the reactive hydroxyl in the 6 position is first blocked, as by an ester group, prior to the chlorination of the hydroxyls in the 4, 1' and 6' positions, followed by hydrolysis to remove the ester substituent to produce sucralose. Several of such synthesis routes involve tin-mediated syntheses of sucrose-6-esters. Illustrative are the tin-mediated routes disclosed by Navia (U.S. Pat. No. 4,950,746), Neiditch et al. (U.S. Pat. No. 5,023,329), Walkup et al. (U.S. Pat. No. 5,089,608--"Walkup et al.-I"), and Sankey et al., U. S. patent application Ser. No. 08/030,930, filed Mar. 12, 1993.
The sucrose-6-esters produced by the above-cited synthesis routes are typically chlorinated by the process of Walkup et al., U.S. Pat. No. 4,980,463 ("Walkup et al.-II"). The chlorination process produces as a product a sucralose-6-ester, such as 4,1',6'-trichloro-4,1',6'-trideoxygalactosucrose-6-acetate ("TGS-6-Ac"--when the sucralose-6-ester is the acetate ester) in solution in a tertiary amide, typically N,N-dimethylformamide ("DMF"). In one aspect, this invention provides a process for the recovery of the TGS-6-ester from the solution in tertiary amide that is the product of the chlorination process of Walkup et al.-II.